Recent work in our laboratory has given us insights into the tissue interactions involved in the determination of embryonic retina and lens. In addition we have initiated studies on the genes regulating these events and propose here to continue this work, with a long term aim of defining the sequence of genetic steps leading to vertebrate eye determination. Our first goal concerns the gamma-crystallin genes in Xenopus embryos, the terminal gene family should allow us to focus in on key promoter sequences controlling the interesting expression patterns we see for these gene (including in one case an intriguing, but unexpected, expression in the hindbrain). The remainder of our work will involve studies of both Xenopus and mouse embryos, with the goal of clarifying the function of several regulatory gene families likely to be important in earlier events in eye determination. A primary goal will be to begin to define a putative genetic hierarchy leading to eye formation. The later issue will be examined first in mice, by a study of the Small-eye mouse mutant, in which eye development is grossly disturbed, and which has recently been shown to result from inactivation of the pax-6 homeobox-containing gene. Studies are planned to establish where this gene lies in the proposed hierarchy by examining in mutant eye determination. In order to examine comparable issues in Xenopus embryos it will be important to study the expression in Xenopus of homologs of several mouse genes, pax-6 and others, and to continue our studies of a new class of putative transcriptional regulatory genes containing HMG-box motifs related to those in the mouse sry gene. One member of this class is expressed only in the forebrain and retina and is a likely candidate for a key relationships among putative regulatory genes in Xenopus embryos, taking advantage of approaches that are especially well suited to this organism, and that should complement experiments with mouse embryos.